Introduction: Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid that is synthesized within the central nervous system, mostly from its parent compound gamma amino butyric acid (GABA).
GHB acts as a neuromodulator/neurotransmitter to affect neuronal activity of other neurotransmitters and so, to stimulate the release of growth hormone.
Its sodium salt (sodium oxybate: SXB) was approved by the Food and Drug Administration (FDA) for the treatment of narcolepsy.
SXB has shown to improve disrupted sleep and increase NR3 (slow-wave restorative) sleep in patients with narcolepsy.
It is rapidly absorbed and has a plasma half-life of 30 – 60 minutes, necessitating twice-nightly dosing.
Most of the observed effects of SXB result from binding to GABA-B receptors.
Areas covered: Several randomized, controlled trials demonstrated significantly improved fibromyalgia (FM) symptoms with SXB.
As seen in narcolepsy trials, SXB improved sleep of FM patients, increased slow-wave sleep duration as well as delta power, and reduced frequent night-time awakenings.
Furthermore, FM pain and fatigue was consistently reduced with nightly SXB over time.
Commonly reported adverse events included headache, nausea, dizziness and somnolence.
Despite its proven efficacy, SXB did not receive FDA approval for the management of FM in 2010, mostly because of concerns about abuse. [Sodium Oxybate is the infamous ‘date rape drug.’]
Expert opinion: Insomnia, fatigue and pain are important clinical FM symptoms that showed moderate improvements with SXB in several large, well-designed clinical trials.
Because of the limited efficacy of currently available FM drugs additional treatment options are needed. In particular, drugs like SXB – which belong to a different drug class than other Food and Drug Administration (FDA)-approved FM medications such as pregabalin, duloxetine and milnacipran – would provide a much-needed addition to presently available treatment options.
However, the FDA has set the bar high for future SXB re-submissions, with requirements of superior efficacy and improved risk mitigation strategies.
At this time, no future FDA submission of SXB for the fibromyalgia indication is planned.
[Note: Xyrem is a costly drug, at a cost per patient of about $30,000 per year. The maker, Jazz Pharmaceuticals, has hiked the price 220% since 2008, including an increase of 22% in November 2010 and another 18% in April 2011, according to www.investors.com – with an additional 71% boost reportedly projected “by the end of 2014.”
Source: Expert Opinion on Pharmacotherapy, Jun 16, 2011. PMID:21679091, by Staud R, University of Florida – medicine, Gainesville, Florida, USA [Email: Roland.Staud@medicine.ufl.edu]